Early central line-associated blood stream infections in children with cancer pose a risk for premature catheter removal.

AIM: This study examined the clinical characteristics of central line-associated blood stream infections occurring within 30 days after insertion versus later infections in paediatric cancer patients and the subsequent risk for premature catheter removal. METHODS: This was a retrospective study of children aged 0-18 years who were diagnosed with cancer from 2013 to 2014 at the Astrid Lindgren Children Hospital, Sweden. Clinical and microbiology data for each patient were collected for 365 days after the central venous catheter (CVC) was inserted. RESULTS: During the study period, 154 children received a CVC. The overall incidence of central line associated blood stream infections was 2.0 per 1000 catheter days. A total of 108 infectious episodes were identified in 44/154 (29%) patients. Of those, 15/44 children (29%) had an early infection within 30 days and alpha-haemolytic Streptococci and coagulase-negative Staphylococci dominated. Children with early infections were more likely to have a haematological malignancy and to need premature removal of the CVC due to repeated infections. CONCLUSION: We observed a high prevalence of early CVC associated blood stream infection mainly in patients with haematological malignancies. Our study highlights the importance of preventive measures in reducing infections in paediatric cancer patients.

Button battery injury causing an aorto-oesophageal fistula in a 1-year-old child - Sengstaken-Blakemore tube, a life-saving bridge during surgery.

ABBREVIATION: AEF: aorto-oesophageal fistula;BB: button battery;CTA: computed tomography angiography;ER: emergency room;GI: gastro-intestinal;SBT: Sengstaken-Blakemore tube.

Increased risk for postoperative periprosthetic fracture in hip fracture patients with the Exeter stem than the anatomic SP2 Lubinus stem.

BACKGROUND: The purpose of this study was to compare the cumulative incidence of postoperative periprosthetic fracture (PPF) in a cohort of femoral neck fracture (FNF) patients treated with two commonly used cemented stems: either a collarless, polished, tapered Exeter stem or the anatomic Lubinus SP2 stem. METHODS: In this retrospective multicenter cohort study of a consecutive series of patients, we included 2528 patients of age 60 years and above with an FNF who were treated with either hemiarthroplasty or total hip arthroplasty using either a polished tapered Exeter stem or an anatomic Lubinus SP2 stem. The incidence of PPF was assessed at a minimum of 2 years postoperatively. RESULTS: The incidence of PPF was assessed at a median follow-up of 47 months postoperatively. Thirty nine patients (1.5%) sustained a PPF at a median of 27 months (range 0-96 months) postoperatively. Two of the operatively treated fractures were Vancouver A (5%), 7 were Vancouver B1 (18%), 10 were Vancouver B2 (26%), 7 were Vancouver B3 (18%), and 13 were Vancouver C (32%). The cumulative incidence of PPF was 2.3% in the Exeter group compared with 0.7% in the SP2 group (p < 0.001). The HR was 5.4 (95% CI 2.4-12.5, p < 0.001), using the SP2 group as the denominator. CONCLUSIONS: The Exeter stem was associated with a higher risk for PPF than the Lubinus SP2 stem. We suggest that the tapered Exeter stem should be used with caution in the treatment of FNF. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov (identifier: NCT03326271).

Experimental extracorporeal membrane oxygenation reduces central venous pressure: an adjunct to control of venous hemorrhage?

BACKGROUND: Venoarterial ECMO has been utilized in trauma patients to improve oxygenation, particularly in the setting of pulmonary contusions and ARDS. We hypothesized that venoarterial ECMO could reduce the central venous pressure in the trauma scenario, thus, alleviating major venous hemorrhage. METHODS: Ten swine were cannulated for venoarterial ECMO. Central venous pressure, mean arterial pressure, portal vein pressure and portal vein flow were recorded at three different flow rates in both a hemodynamic normal state and a setting of increased central venous pressure and right ventricular load, mimicking acute lung injury. RESULTS: Venoarterial ECMO reduced the central venous pressure (CVP( sup)) from 9.4+/-0.8 to 7.3+/-0.7 mmHg (p<0.01) and increased the mean arterial pressure from 103+/-8 to 119+/-10 mmHg (p<0.01) in the normal hemodynamic state. In the state of increased right ventricular load, the CVP(sup) declined from 14.3+/-0.4 to 11.0+/-0.7mmHg (p<0.01) and the mean arterial pressure (MAP) increased from 66+/-6 to 113 +/-5 mmHg (p<0.01). CONCLUSION: Venoarterial ECMO reduces systemic venous pressure while maintaining or improving systemic perfusion in both a normal circulatory state and in the setting of increased right ventricular load associated with acute lung injury. ECMO may be a useful tool in reducing blood loss during major venous hemorrhage in both trauma and selected elective surgery.

Increase in hippocampal volume after electroconvulsive therapy in patients with depression: a volumetric magnetic resonance imaging study.

BACKGROUND: Major depression has traditionally been regarded as a neurochemical disease, but findings of a decreased hippocampal volume in patients with depression have turned the pathophysiological focus toward impairments in structural plasticity. The mechanisms of action of the most effective antidepressive treatment, electroconvulsive therapy (ECT), still remains elusive, but recent animal research has provided evidence for a cell proliferative effect in the hippocampus. The aim of this prospective study was to determine if hippocampal volume changes after ECT in patients with depression. METHODS: Twelve patients with depression and ongoing antidepressive pharmacological treatment were investigated with clinical ratings and 3 T magnetic resonance imaging within 1 week before and after the ECT series. Each hippocampus was manually outlined on coronal slices, and the volume was calculated. RESULTS: The left as well as the right hippocampal volume increased significantly after ECT. CONCLUSIONS: The hippocampal volume increases after ECT, supporting the hypothesis that hippocampus may play a central role in the treatment of depression.

The stability of alexithymia during work in a high-stress environment: a prospective study of Swedish peacekeepers serving in Kosovo.

We applied a prospective design to reinvestigate the issue whether the sub-domains of alexithymia could be considered stable traits or distress-related states. Assessments of alexithymia and subjective distress were conducted before deployment to Kosovo in a sample of male peacekeepers. A second assessment was conducted approximately six months later during the final phase of service. The results showed evidence of moderate to high relative stability in all alexithymic sub-domains. It was also found that a relative change in subjective distress predicted a relative change in difficulty identifying feelings and difficulty describing feelings but not in externally oriented thinking. We suggest therefore that the alexithymic sub-domains could be considered relatively stable traits but that the level of difficulty identifying and describing feeling varies with the level of subjective distress.

Pathogenic copy number variants are detected in a subset of patients with gastrointestinal malformations.

BACKGROUND: Gastrointestinal atresias and urological defects are main causes of pediatric surgery in infants. As copy number variants (CNVs) have been shown to be involved in the development of congenital malformations, the aim of our study was to investigate the presence of CNVs in patients with gastrointestinal and urological malformations as well as the possibility of tissue-specific mosaicism for CNVs in the cohort. METHODS: We have collected tissue and/or blood samples from 25 patients with anorectal malformations, esophageal atresia, or hydronephrosis, and screened for pathogenic CNVs using array comparative genomic hybridization (array-CGH). RESULTS: We detected pathogenic aberrations in 2/25 patients (8%) and report a novel possible susceptibility region for esophageal atresia on 15q26.3. CNV analysis in different tissues from the same patients did not reveal evidence of tissue-specific mosaicism. CONCLUSION: Our study shows that it is important to perform clinical genetic investigations, including CNV analysis, in patients with congenital gastrointestinal malformations since this leads to improved information to families as well as an increased understanding of the pathogenesis.

A structural validation of an inventory based on the Abridged Five Factor Circumplex Model (AB5C).

We investigated the structural validity of an inventory from the International Personality Item Pool (Goldberg et al., 2006) that is based on the Abridged Five Factor Circumplex (AB5C) model. In a Swedish sample of 1,080 subjects using confirmatory factor analysis, we found that the majority of investigated facets had a primary loading on 1 of the 5 personality factors and a secondary loading on another factor. These results provide overall support for the inventory and indirect support for the AB5C model. Some of the problems detected in the inventory appear to be rooted at the item level and may be a result of how the AB5C is operationalized. Thus, the inventory still requires some refinement and is not in its final stage of development. Nevertheless, our preliminary results are very promising, and we believe the AB5C model deserves renewed attention in trait psychology.

Driver-related risk factors of fatal road traffic crashes associated with alcohol or drug impairment.

Fatal road traffic crashes are often related to speeding, non-use of a seatbelt, and alcohol/drug-impaired driving. The aim of this study was to examine associations between driving under the influence of drugs and/or alcohol and driver-related risk factors that have been reported as significantly contributing causes of fatal road traffic crashes. The data were extracted from Norwegian road traffic crash registries and forensic toxicology databases. Drug/alcohol investigated car and van drivers and motorcycle riders fatally injured in road traffic crashes in Norway during 2005-2015 were included in this study (n = 772). Drug and alcohol concentrations corresponding to 0.5 g/kg alcohol in blood were used as the lower limits for categorising drivers/riders as impaired; 0.2 g/kg was the upper limit for being categorised as sober. Associations between driver-related risk factors and impairment from specific substance groups were calculated using multivariable logistic regression, adjusted for other substance groups, age, and sex, and were reported when the confidence intervals did not contain the value 1 or lower. Substances found in concentrations above the impairment limits were mainly alcohol (20%), medicinal drugs (10%: benzodiazepines, opioids, z-hypnotics), stimulants (5%: amphetamines, methylphenidate, and cocaine), and cannabis (4%: THC). The drug/alcohol-impaired drivers had compared to the sober drivers more often been speeding (68% versus 32%), not used a seatbelt (69% versus 30%), and been driving without a valid driver license (26% versus 1%). Logistic regression analysis showed that impairment from alcohol or stimulants (mainly amphetamines) was associated with all three risk factors, medicinal drugs with all except speeding, and impairment from cannabis (THC) with not having a valid driver license. Among motorcycle riders, drug/alcohol impairment was associated with not having a valid driver license and non-use of a helmet. At least one of the risk factors speeding, non-use of a seatbelt/helmet, and driving without a valid license were present among the vast majority of the drug/alcohol-impaired fatally injured drivers and riders, and also among more than half of the fatally injured sober drivers.

Fatally injured drivers in Norway 2005-2015-Trends in substance use and crash characteristics.

Objective: Norway introduced a "Vision Zero" strategy in 2001, using multiple approaches, aiming toward a future in which no one will be killed or seriously injured in road traffic crashes (RTCs). Official statistics show that the number of fatally injured road users has declined substantially from 341 deaths in 2000 to 117 in 2015. In-depth crash investigations of all fatal RTCs started in Norway in 2005. The aim of this study was to investigate whether fatal crash characteristics, vehicle safety features, and prevalence of drugs and/or alcohol among fatally injured drivers and riders has changed during 2005-2015, accompanying the reduction in road fatalities. Methods: Data on all car/van drivers and motorcycle/moped riders fatally injured in RTCs during 2005-2015 were extracted from Norwegian road traffic crash registries and combined with forensic toxicology data. Results: The proportion of cars and motorcycles with antilock braking systems and cars with electronic stability control, increased significantly during the study period. The prevalence of nonuse of seat belts/helmets and speeding declined among both fatally injured drivers and riders. In addition, the prevalence of alcohol declined, though no significant change in the total prevalence of other substances was noted. Conclusion: The observed changes toward more safety installations in cars and motorcycles and lower prevalence of driver-related risk factors like alcohol use, speeding, and nonuse of seat belts/helmets among fatally injured drivers/riders may have contributed to the decrease in road traffic deaths.

Baseline verbal fluency performance as predictor of state anxiety during a live hand-grenade throwing exercise - A prospective study of Swedish military conscripts.

BACKGROUND: We investigated whether individual differences in baseline executive control capacity could predict state anxiety during a potentially life-threatening situation. METHODS: 19 Swedish military conscripts were assessed during two measurement occasions. During a baseline measurement, data regarding performance on a letter fluency task and state anxiety were assessed. During a second measurement, performed immediately prior to participation in a live hand-grenade throwing exercise, data regarding state anxiety was assessed. All participants were male, right-handed and had fulfilled 12 years of education. RESULTS: The level of state anxiety was significantly increased between the two measurement occasions (p < .01). Both the number of words produced (beta = -.37; p < .05) and the number of perseveration made (beta = .43; p < .05) on the verbal fluency task predicted, while controlling for state anxiety at baseline, the level of experienced state anxiety during the threatening situation. CONCLUSION: Although more research is needed the present finding suggests that individual differences in executive control capacity might be related to emotion regulation ability during acute stressor exposure.

Height-controlled nanowire branches on nanotrees using a polymer mask.

The production of complex three-dimensional dendritic structures is an important step in the application of semiconductor nanowires. One promising method for achieving this is the sequential seeding of multiple generations of epitaxial nanowires using metal seed particles. However, it is difficult to control and predict the position of second and higher generation nanowires with respect to the first generation. Here we demonstrate a procedure for controlling the position of second-generation epitaxial nanowire branches on vertically aligned nanowire trunks. This method uses a spun-on polymer layer that masks first-generation wires to a specified height, preventing the growth of nanowire branches at lower positions as well as new nanowire growth on the substrate. This method appears not to be dependent on the materials or growth system (in this case MOVPE-grown GaP is demonstrated), and hence is likely to be applicable to a variety of materials systems and growth procedures using metal seed particles.

Transcript identification by analysis of short sequence tags--influence of tag length, restriction site and transcript database.

There exist a number of gene expression profiling techniques that utilize restriction enzymes for generation of short expressed sequence tags. We have studied how the choice of restriction enzyme influences various characteristics of tags generated in an experiment. We have also investigated various aspects of in silico transcript identification that these profiling methods rely on. First, analysis of 14 248 mRNA sequences derived from the RefSeq transcript database showed that 1-30% of the sequences lack a given restriction enzyme recognition site. Moreover, 1-5% of the transcripts have recognition sites located less than 10 bases from the poly(A) tail. The uniqueness of 10 bp tags lies in the range 90-95%, which increases only slightly with longer tags, due to the existence of closely related transcripts. Furthermore, 3-30% of upstream 10 bp tags are identical to 3' tags, introducing a risk of misclassification if upstream tags are present in a sample. Second, we found that a sequence length of 16-17 bp, including the recognition site, is sufficient for unique transcript identification by BLAST based sequence alignment to the UniGene Human non-redundant database. Third, we constructed a tag-to-gene mapping for UniGene and compared it to an existing mapping database. The mappings agreed to 79-83%, where the selection of representative sequences in the UniGene clusters is the main cause of the disagreement. The results of this study may serve to improve the interpretation of sequence-based expression studies and the design of hybridization arrays, by identifying short tags that have a high reliability and separating them from tags that carry an inherent ambiguity in their capacity to discriminate between genes. To this end, supplementary information in the form of a web companion to this paper is located at http:// biobase.biotech.kth.se/tagseq.

Associations between driving under the influence of alcohol or drugs, speeding and seatbelt use among fatally injured car drivers in Norway.

Since 2005, all fatal road traffic crashes in Norway have been analyzed in-depth by multidisciplinary investigation teams organized by the Norwegian Public Roads Administration (NPRA). During the period 2005-2010, 608 drivers of cars or vans were killed in road traffic crashes. Blood samples were collected from 372 (61%) of the drivers and analyzed for alcohol and a large number of psychoactive drugs at the Norwegian Institute of Public Health (NIPH). After coupling the analytical results with the NPRA crash database, 369 drivers with a fatal outcome were identified and included. Alcohol or drug concentrations in blood above the legal limits were found in 39.8% of the drivers who were investigated for alcohol or drug impairment; 33.9% had blood alcohol concentrations above 0.5g/L or concentrations of drugs above the equivalent Norwegian legal impairment limits or concentrations of amphetamines above 200µg/L. Among drivers with a fatal outcome who had been impaired by alcohol or drugs, 64.6% were unbelted and 71.7% were speeding when the crash occurred; whereas 24.2% and 33.2% of the sober drivers were unbelted or speeding, respectively. Statistically significant associations were found between impairment by alcohol or amphetamines and driving unbelted or speeding. Excessive speeding is one of the main reasons for road traffic crashes and together with being unbelted the main reasons for a fatal outcome. This behavior might in many cases be due to increased risk-taking or negligence of safety measures as a result of alcohol or drug use.

Gene expression analysis by signature pyrosequencing.

We describe a novel method for transcript profiling based on high-throughput parallel sequencing of signature tags using a non-gel-based microtiter plate format. The method relies on the identification of cDNA clones by pyrosequencing of the region corresponding to the 3'-end of the mRNA preceding the poly(A) tail. Simultaneously, the method can be used for gene discovery, since tags corresponding to unknown genes can be further characterized by extended sequencing. The protocol was validated using a model system for human atherosclerosis. Two 3'-tagged cDNA libraries, representing macrophages and foam cells, which are key components in the development of atherosclerotic plaques, were constructed using a solid phase approach. The libraries were analyzed by pyrosequencing, giving on average 25 bases. As a control, conventional expressed sequence tag (EST) sequencing using slab gel electrophoresis was performed. Homology searches were used to identify the genes corresponding to each tag. Comparisons with EST sequencing showed identical, unique matches in the majority of cases when the pyrosignature was at least 18 bases. A visualization tool was developed to facilitate differential analysis using a virtual chip format. The analysis resulted in identification of genes with possible relevance for development of atherosclerosis. The use of the method for automated massive parallel signature sequencing is discussed.

Single-vector three-frame expression systems for affinity-tagged proteins.

An effort is presented to create expression vectors which would allow expression of an inserted gene fragment in three reading frames in a single vector from a single promoter but with three separate ribosome binding sites (RBS). Each expression frame would generate an in-frame fusion with an affinity tag to allow efficient recovery of the produced fusion proteins. In the first generation vector, three identical polyhistidyl tags (His(6)) were used as affinity tags for the three expression frames. In the second generation vector, three different tags, an albumin binding domain derived from streptococcal protein G, an IgG binding Staphylococcus aureus protein A-derived domain (Z) and a His(6) tag, were employed to allow frame-specific affinity recovery. To evaluate the systems, model genes have been inserted in three different frames in both vectors. The first vector was demonstrated to produce fusion proteins in all three frames, whereas for the second, with a much wider spacing between the RBSs and affinity tags, expression could only be demonstrated from the first two translational start sites. For both systems, the first translation start was found to be significantly favored over the others. Nevertheless, we believe that the presented results represent the first successful attempt to create single-vector three-frame expression systems, a concept that could become valuable in future combined cloning-expression vectors.

A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk.

Currently used anticoagulants prevent thrombosis but increase bleeding. We show an anticoagulation therapy without bleeding risk based on a plasma protease factor XII function-neutralizing antibody. We screened for antibodies against activated factor XII (FXIIa) using phage display and demonstrated that recombinant fully human antibody 3F7 binds into the FXIIa enzymatic pocket. 3F7 interfered with FXIIa-mediated coagulation, abolished thrombus formation under flow, and blocked experimental thrombosis in mice and rabbits. We adapted an extracorporeal membrane oxygenation (ECMO) cardiopulmonary bypass system used for infant therapy to analyze clinical applicability of 3F7 in rabbits. 3F7 provided thromboprotection as efficiently as heparin, and both drugs prevented fibrin deposition and thrombosis within the extracorporeal circuit. Unlike heparin, 3F7 treatment did not impair the hemostatic capacity and did not increase bleeding from wounds. These data establish that targeting of FXIIa is a safe mode of thromboprotection in bypass systems, and provide a clinically relevant anticoagulation strategy that is not complicated by excess bleeding.

Car crash fatalities associated with fire in Sweden.

OBJECTIVE: To study the epidemiology and causes of death in fatal car crashes on Swedish roads in which the victim's vehicle caught fire. METHODS: The data set is from the Swedish Transport Administrations in-depth studies of fatal crashes 1998-2008. Autopsies from all cases provided data on injuries, toxicological analyses, and cause of death. RESULTS: In total, 181 people died in 133 burning cars, accounting for 5 percent of all deaths in passenger cars, sport utility vehicles, vans, and minibuses during 1998 to 2008. The cause of death for a third of the victims was fire related, as burns and/or smoke inhalation injuries, with no fatal trauma injuries. Twenty-five of these 55 deaths were persons 19 years or younger and included 15 of 18 rear seat deaths. Over half of the 181 deaths were in vehicles that had collided with another vehicle and, of these cases, half were killed in collisions with heavy vehicles. The percentage of drivers with illegal blood alcohol concentrations (27%) and suicides (5.5%) were not higher than in other fatal crashes on Swedish roads. The ignition point of the fire was indicated in only half of the cases and, of those, half started in the engine compartment and one fourth started around the fuel tank or lines. CONCLUSIONS: Car fires are a deadly postcrash problem. Reducing this risk would be primarily a responsibility for the automotive industry. A multifactor approach could be considered as follows: risk-reducing design, insulation, reduced flammability in motor compartment fluids and plastics, and automatic fire extinguishing equipment. Inspiration could be found in how, for example, the auto racing and aviation industries handle this problem.

The interaction between baseline trait anxiety and trauma exposure as predictor of post-trauma symptoms of anxiety and insomnia.

In this study a prospective design was used to investigate the interaction between baseline trait anxiety and exposure to traumatic situations on post-trauma symptoms of anxiety and insomnia in a sample of Swedish peacekeeping soldiers serving in Kosovo. The result showed that pre-trauma trait anxiety interacted with exposure to traumatic situations predicting a higher post-trauma distress. Further, baseline trait anxiety and baseline symptoms of anxiety and insomnia predicted post-trauma symptoms of anxiety and insomnia. The results support a diathesis stress model in which high trait anxiety interacts with trauma exposure in the elicitation of anxiety-related distress but the study needs to be replicated before further conclusions can be drawn.

Few electron double quantum dots in InAs/InP nanowire heterostructures.

We report on fabrication of double quantum dots in catalytically grown InAs/InP nanowire heterostructures. In the few-electron regime, starting with both dots empty, our low-temperature transport measurements reveal a clear shell structure for sequential charging of the larger of the two dots with up to 12 electrons. The resonant current through the double dot is found to depend on the orbital coupling between states of different radial symmetry. The charging energies are well described by a capacitance model if next-neighbor capacitances are taken into account.